Cervical cancer, the most common female cancer in India, is a preventable malignancy. The recent recognition that genital tract infection with high-risk human papillomavirus (HPV) is the primary cause of cervical cancer has led to HPV-based cancer prevention strategies. The proposed project will be carried out in Medchal Mandal, a rural community near Hyderabad, in Andhra Pradesh, India. Its broad objectives are to help identify the optimum cervical cancer screening method for rural India and to evaluate the viral and cellular markers of progression to cancer. It is anticipated that almost all of the approximately 12,000 eligible women in this community (30 years old or older) will each be screened for cervical cancer with four methods: Pap smear, visual inspection of the cervix, HPV DNA in cervix, and HPV DNA in self-collected swabs. Women with abnormal results in any one or more screens will be colposcoped and biopsied if necessary. Those found to have high-grade lesions or cervical cancer will be treated. Women who have abnormal screens but do not require treatment, as well as women without abnormal screens, will be monitored annually for an additional four years for development of high grade lesions or cervical cancer. It is estimated that more than 200 women with high-grade lesions and about 20-30 women with cervical cancer will be identified during the study period. Appropriate biological specimens will be collected to meet the following specific aims: (a) to compare the four screening methods for their ability to identify prevalent disease and to predict incident disease, (b) to characterize viral genotype, viral variants, viral persistence, viral load and integration for their role in disease progression, (c) to evaluate cellular markers such as p16 over-expression, loss of FHIT expression, gain of chromosome 3q, and altered patterns of methylation for their role in disease progression, and (d) to correlate the viral and cellular markers of disease progression. The detailed investigation of viral and cellular markers of cervical cancer in a community-based population may aid in the establishment of more detailed models of cervical cancer development. Broadly, the integrated observations from this study may help identify screening methods and biological markers that may be valuable for cervical cancer prevention.